Water → Benzyl 3-(hydroxymethyl)piperidine-1-carboxylate

HRID 892244Notes

Reaction equation

HRID 892244 reaction equation
C([O:3][C:4]([C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[CH2:7]1)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C1COCC1>[CH2:15]([O:14][C:12]([N:8]1[CH2:9][CH2:10][CH2:11][CH:6]([CH2:4][OH:3])[CH2:7]1)=[O:13])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 16091193(R)-1-Benzyl 3-ethyl piperidine-1,3-dicarboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 2776577Benzyl 3-(hydroxymethyl)piperidine-1-carboxylateYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Piperidine-1,3-dicarboxylic acid 1-benzyl ester 3-ethyl ester (7) (1.5 g, 5.83 mmol) was dissolved in 5.8 mL of anhydrous THF, and the reaction was stirred under N2 at −5° C. while lithium aluminum hydride dissolved in THF (7.0 mL, 1.0M) was added dropwise by addition funnel over 30 minutes. When the reaction was complete by TLC (10 min.), H2O (0.6 mL), then 10% NaOH (1.5 mL), then H2O (0.6 mL) were added, and the reaction was stirred for about 45 minutes. The salts were removed by filtration and the solution was dried with sodium sulfate, filtered, and concentrated. The crude material was purified using an ISCO CombiFlash flash column (silica, 80:20 Hexane:EtOAc to 40:60 Hexane:EtOAc) to achieve 1.24 g of pure 8 (66% yield).

Workup

  1. additionwas added dropwise by addition funnel over 30 minutes
  2. customThe salts were removed by filtration
  3. dry with materialthe solution was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified

Sources & evidence

ORD record
ord-3808c397ff4d4bf28619167b1e3c1e07
Source dataset
uspto-grants-2006_02
Patent number
US07005524B2

Reaction notes

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